Lithium trifluoromethanesulphonate

Acute Toxicity: oral

Administrative data

Endpoint:

acute toxicity: oral

Type of information:

experimental study

Adequacy of study:

key study

Study period:

From 28-July-2016 to 11-October-2016

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

guideline study

Remarks:

GLP compliant

Data source

Reference

Reference Type:

study report

Title:

Unnamed

Year:

2016

Report date:

2016

Materials and methods

Test guideline

Test guideline 1

Qualifier:

according to guideline

Guideline:

OECD Guideline 423 (Acute Oral toxicity - Acute Toxic Class Method)

Deviations:

yes

Remarks:

1. Deviations from the maximum level of daily mean relative humidity occured. 2. No clinical signs were registered for animal no. 1 on Day 8. Considered not to effect study reliability.

Test guideline 2

Qualifier:

according to guideline

Guideline:

EU Method B.1 tris (Acute Oral Toxicity - Acute Toxic Class Method)

Deviations:

yes

Remarks:

1. Deviations from the maximum level of daily mean relative humidity occured. 2. No clinical signs were registered for animal no. 1 on Day 8. Considered not to effect study reliability.

Test guideline 3

Qualifier:

according to guideline

Guideline:

EPA OPPTS 870.1100 (Acute Oral Toxicity)

Test guideline 4

Qualifier:

according to guideline

Guideline:

other: JMAFF Guidelines (2000)

Version / remarks:

including the most recent revisions

GLP compliance:

yes (incl. QA statement)

Test type:

acute toxic class method

Limit test:

yes

Test material

Test material information

Constituent 1

Reference substance name:

Lithium trifluoromethanesulphonate

EC Number:

251-528-5

EC Name:

Lithium trifluoromethanesulphonate

Cas Number:

33454-82-9

Molecular formula:

CHF3O3S.Li

IUPAC Name:

lithium trifluoromethanesulphonate

Test material form:

solid: particulate/powder

Details on test material:

See confidential details on test material

Specific details on test material used for the study:

STABILITY AND STORAGE CONDITIONS OF TEST MATERIAL:
- At room temperature container flushed with nitrogen, desiccated

Test animals

Species:

rat

Strain:

Wistar

Sex:

female

Details on test animals or test system and environmental conditions:

TEST ANIMALS:
- Source: Charles River Deutschland, Sulzfeld, Germany
- Females nulliparous and non-pregnant
- Age at study initiation: ca. 8-10 weeks old
- Weight at study initiation: body weight variation did not exceed +/- 20% of the sex mean
- Fasting period before study: Animals were deprived of food overnight prior to dosing and until 3-4 hours after administration of the test item. Water was available ad libitum.
- Housing: group housing of 3 animals per cage in labeled Makrolon cages (MIV type; height 18 cm) containing sterilized sawdust as bedding material and paper as cage-enrichment
- Diet: ad libitum
- Water ad libitum
- Acclimatation period: at least 5 days before start of treatment under laboratory conditions

DETAILS OF FOOD AND WATER QUALITY:
- Feed: Free access to pelleted rodent diet (SM R/M-Z from SSNIFF® Spezialdiäten GmbH, Soest, Germany)
- Water: Free access to tap water
Diet, water, bedding and cage enrichment evaluation for contaminants and/or nutrients was performed according to facility standard procedures.

ENVIRONMENTAL CONDITIONS:
- Temperature (°C): 18-24
- Humidity (%): 40-70
- Air changes (per hr): at least 10
- Photoperiod (hrs dark / hrs light): 12/12

Administration / exposure

Route of administration:

oral: gavage

Vehicle:

water

Details on oral exposure:

Single dosage on Day 1 using plastic feeding tubes

Doses:

First step: 2000 mg/kg (10 mL/kg) body weight.
Second step: 300 mg/kg (10 mL/kg) body weight.

No. of animals per sex per dose:

3

Control animals:

no

Details on study design:

- Duration of observation period following administration: 14 days
- Frequency of observations and weighing:
- Mortality/Viability: Twice daily. The time of death was recorded as precisely as possible.
- Body weights: Days 1 (pre-administration), 8 and 15 and at death (if found dead after Day 1).
- Clinical signs: At periodic intervals on the day of dosing (Day 1) and once daily thereafter, until Day 15. The signs were graded according to fixed scales and the time of onset, degree and duration were recorded:
- Maximum grade 4: grading slight (1) to very severe (4)
- Maximum grade 3: grading slight (1) to severe (3)
- Maximum grade 1: presence is scored (1)
- Necropsy of survivors performed: yes
- Macroscopic examination was performed on the day of death or after terminal sacrifice (Day 15).

Statistics:

No statistical analysis was performed (the method used is not intended to allow the calculation of a precise LD50 value).

Results and discussion

Effect levels

Effect levels 1

Sex:

female

Dose descriptor:

LD50

Effect level:

> 300 - < 2 000 mg/kg bw

Effect levels 2

Sex:

female

Dose descriptor:

LD50 cut-off

Effect level:

1 000 mg/kg bw

Remarks on result:

other: According to the OECD 423 test guideline

Mortality:

At 2000 mg/kg, two animals were found dead on Days 3 and 5.
At 300 mg/kg, no mortality occurred.

Clinical signs:

other: At 2000 mg/kg, hunched posture, piloerection, lean appearance, dehydrated appearance, abnormal gait, shallow respiration and/or diarrhoea were noted for all animals between Days 1 and 4. At 300 mg/kg piloerection and/or restless behaviour were noted for a

Other findings:

- Macroscopic findings:
At 2000 mg/kg, abnormalities of the lungs (pale discoloration), uterus (greenish discoloration), spleen (reduced size) and/or stomach (several, dark red, foci, glandular mucosa) were noted for the animals that were found dead.
At 300 mg/kg, macroscopic post mortem examination did not reveal any abnormalities.

- Other observations:
Cannibalism was noted for one of the animals found dead. This was considered not toxicologically relevant.

Applicant's summary and conclusion

Interpretation of results:

Category 4 based on GHS criteria

Conclusions:

The oral LD50 value of Lithium Trifluoromethanesulfonate in Wistar rats was established to be within the range of 300-2000 mg/kg body weight.
According to the OECD 423 test guideline, the LD50 cut-off value was considered to be 1000 mg/kg body weight.

Based on these results:
- according to the Globally Harmonized System of Classification and Labelling of Chemicals (GHS) of the United Nations (2015) (including all amendments), Lithium Trifluoromethanesulfonate should be classified as: harmful if swallowed (Category 4) for acute toxicity by the oral route.
- according to the Regulation (EC) No 1272/2008 on classification, labelling and packaging of items and mixtures (including all amendments), Lithium Trifluoromethanesulfonate should be classified as Category 4 and should be labeled as H302: Harmful if swallowed.

Executive summary:

The assessment of acute oral toxicity of Lithium Trifluoromethanesulfonate in the rat (Acute Toxic Class Method) was carried out, under GLP compliance, based on the guidelines described in: OECD No.423 (2001), EU Method B1 tris, EPA OPPTS 870.1100 (2002) and JMAFF Guidelines (2000), including the most recent revisions.

Initially, Lithium Trifluoromethanesulfonate was administered by oral gavage to three female Wistar rats at 2000 mg/kg body weight. In a stepwise procedure two additional groups of three females were dosed at 300 mg/kg body weight. All animals were subjected to daily observations and weekly determination of body weight. Macroscopic examination was performed on the day of death or after terminal sacrifice (Day 15).

At 2000 mg/kg, two animals were found dead on Days 3 and 5.

At 300 mg/kg, no mortality occurred.

At 2000 mg/kg, hunched posture, piloerection, lean appearance, dehydration, abnormal gait, shallow respiration and/or diarrhoea were noted for all animals between Days 1 and 4.

At 300 mg/kg piloerection and/or restless behaviour were noted for all animals on Day 1.

The mean body weight gain shown by the animals over the study period was considered to be normal.

At 2000 mg/kg, abnormalities of the lungs (pale discoloration), uterus (greenish discoloration), spleen (reduced size) and/or stomach (several, dark red, foci, glandular mucosa) were noted for the animals that were found dead.

At 300 mg/kg, macroscopic post mortem examination did not reveal any abnormalities.

The oral LD50 value of Lithium Trifluoromethanesulfonate in Wistar rats was established to be within the range of 300-2000 mg/kg body weight.

According to the OECD 423 test guideline, the LD50 cut-off value was considered to be 1000 mg/kg body weight.

Based on these results:

- according to the Globally Harmonized System of Classification and Labelling of Chemicals (GHS) of the United Nations (2015) (including all amendments), Lithium Trifluoromethanesulfonate should be classified as: harmful if swallowed (Category 4) for acute toxicity by the oral route.

- according to the Regulation (EC) No 1272/2008 on classification, labelling and packaging of items and mixtures (including all amendments), Lithium Trifluoromethanesulfonate should be classified as Category 4 and should be labeled as H302: Harmful if swallowed.